Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1

• Published in: Experimental neurology 2024-09, Vol.379, p.114844, Article 114844
• Main Authors: Zhai, Chenyuan, Wang, Zun, Cai, Jili, Fang, Lu, Li, Xiangzhe, Jiang, Kunmao, Shen, Ying, Wang, Yu, Xu, Xingjun, Liu, Wentao, Wang, Tong, Wu, Qi
• Format: Article
• Language: English
• Subjects: LRP-1; Magnetic stimulation; Microglia; Myelin debris; Phagocytosis; Spinal cord injury
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2024.114844

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats. [Display omitted] •We found that repeated magnetic stimulation on the site of spinal injury was able to promote the clearance of myelin debris, improve the spinal cord microenvironment and promote the recovery of SCI function.•We found that the repeated magnetic stimulation could enhance microglial phagocytosis to remove myelin debris probably through the inhibition of LRP-1 shedding.•This study explores new targets for improving the spinal cord injury microenvironment by repeated magnetic stimulation and provides a new theoretical basis for clinical bio-electromagnetism to promote central nervous system functional recovery.